Antiviral potency of lupane and oleanane alkynyl-derivatives against human cytomegalovirus and papillomavirus.

A library of 18 structurally diverse semisynthetic lupane, oleanane, and ursane types triterpenoids, including C19- or C28-(1,2,3-triazolyl)- and aminomethylated derivatives obtained by the «click» reaction with various aromatic and sugar azides or by Mannich reaction with secondary amines, were tested for antiviral activity against HCMV, HSV-1, and HPV-11 types. C28-Triazolyl-derivative with a benzyl substituent of 2,3-indolo-oleanolic acid was the most active against the HCMV virus with EC < 0.05 (SI > 81).

Development of New Antimicrobial Oleanonic Acid Polyamine Conjugates.

A series of oleanolic acid derivatives holding oxo- or 3--polyamino-3-deoxy-substituents at C3 as well as carboxamide function at C17 with different long chain polyamines have been synthesized and evaluated for antimicrobial activities. Almost all series presented good to moderate activity against Gram-positive , and bacteria with minimum inhibitory concentration (MIC) values from 3.125 to 200 µg/mL.

Diastereoselective Synthesis of Triterpenoid 1,2,4-Trioxolanes by Griesbaum Co-ozonolysis.

Diastereoselective synthesis of triterpenoid 1,2,4-trioxolanes by Griesbaum co-ozonolysis was shown for the first time. Ozonolysis of 2-methoxyoximes (--isomers mixture) of allobetulin or methyl oleanoate with CF-ketones resulted in asymmetrical spiro-1,2,4-trioxolanes as mixtures of diastereomers in yields up to 80-85%. The configuration of the spiro-C-2 center of individual ozonides was determined by 2D NMR spectra and X-ray crystallographic analysis.

Structural modifications of 2,3-indolobetulinic acid: Design and synthesis of highly potent α-glucosidase inhibitors.

A series of nineteen nitrogen-containing lupane triterpenoids was obtained by modification of C2, C3, C20 and C28 positions of betulonic acid and their α-glucosidase inhibiting activity was investigated. Being a leader compound from our previous study, 2,3-indolo-betulinic acid was used as the main template for different modifications at C-(28)-carboxyl group to obtain cyano-, methylcyanoethoxy-, propargyloxy- and carboxamide derivatives. 20-Oxo- and 29-hydroxy-20-oxo-30-nor-analogues of 2,3-indolo-betulinic acid were synthesized by ozonolysis of betulonic acid followed by Fischer indolization reaction.

Synthesis of A-ring quinolones, nine-membered oxolactams and spiroindoles by oxidative transformations of 2,3-indolotriterpenoids.

This paper describes an access to new nitrogen-containing heterocyclic triterpenoids by the reaction of 2,3-indolotriterpenoids with ozone and dimethyldioxirane. The oxidation of indolo-fused 28-oxo-allobetulin or methyl platanoate with ozone led to a mixture of a quinolone as the major product and a nine-membered 2,3-seco-2-oxolactam and three different types of spiroindoles as byproducts. The formation of quinolone and 2,3-seco-2-oxolactam derivatives could be explained by the standard 1,3-dipolar cycloaddition of ozone to the C2(3)-double bond of the triterpene core similar to the products observed in the ozonolysis of indoles in the Witkop-Winterfeldt oxidation (WWO).

Synthesis and antimalarial activity of 3'-trifluoromethylated 1,2,4-trioxolanes and 1,2,4,5-tetraoxane based on deoxycholic acid.

A series of new steroidal peroxides - 3'-trifluoromethylated 1,2,4-trioxolanes and 1,2,4,5-tetraoxanes based on deoxycholic acid were prepared via the reactions of the Griesbaum coozonolysis and peroxycondensation, respectively. 1,2,4-Trioxolanes were synthesized by the interaction of methyl O-methyl-3-oximino-12α-acetoxy-deoxycholate with CFC(O)CH or CFC(O)Ph and O as the mixtures of four possible stereoisomers at ratios of 1:2:2:1 and in yields of 50% and 38%, respectively. The major diastereomer of methyl 12α-acetoxy-5β-cholan-24-oate-3-spiro-5'-(3'-methyl-3'-trifluoromethyl-1',2',4'-trioxolane) was isolated via crystallization of a mixture of stereoisomers from hexane and its (3S,3'R)-configuration was determined using X-ray crystallographic analysis.

Stereospecific Oxidation of Diacetoxyheterobetulin with Ozone and Dimethyldioxirane.

Stereospecific oxidation of diacetoxyheterobetulin with ozone and dimethyldioxirane led to 3β,28-diacetoxy-18α,19βH-urs-20α,21α-epoxide with yields of 79% and 87%, respectively. Oxidation with ozone was not selective and gave two minor products containing 2lα-hydroxy-20(30)-ene and 21a-hydroxy-20β,28-epoxy-fragments in ring E. The structures of 3β,28-diacetoxy-18α,19βH-urs-20α,21α-epoxide and 3β-diacetoxy-21α-hydroxy-20β,28-epoxy-18α,19βH-ursane were confirmed by X-ray analysis for the first time.

Inhibition of Alpha-Glucosidase by Synthetic Derivatives of Lupane, Oleanane, Ursane and Dammarane Triterpenoids.

A variety of new and earlier synthesized lupane, oleanane, ursane and dammarane triterpenoids have been investigated for their inhibitory activity against α-glucosidase. 2,3-Indole-21 β-acetyl-20β,28-epoxy-18α,19βH-ursane and 3-oxo-3A-homo-3a-aza-20(S)-hydroxydammar-24(25)-ene were synthesized for the first time. The compounds 3, 4, 8-11 and 14 demonstrated strong in vitro inhibitory activity towards α-glucosidase with IC₅₀ values of 37.